Anti-cancer agents in medicinal chemistry最新文献

{"title":"Bioactive Constituents and Potential Cytotoxic Activities of Green Microalgae: Desmodesmus spp. from a Jordanian Isolate.","authors":"Lidia K Al-Halaseh, Ali Al-Samydai, Mais A Sweiss, Moath Al-Qaraleh, Diala Akram Alsoub, Simone Carradori","doi":"10.2174/0118715206453560260313042524","DOIUrl":"https://doi.org/10.2174/0118715206453560260313042524","url":null,"abstract":"<p><strong>Introduction/objectives: </strong>Conventional anticancer agents have numerous limitations, and developing innovative agents to treat cancer places a heavy burden on the global health economy. The current study aims to explore sustainable and alternative sources for cancer therapy.</p><p><strong>Objectives: </strong>This study aims to investigate the phytoconstituents and biologically active compounds in green microalgae and to explore their potential cytotoxicity.</p><p><strong>Methods: </strong>Algae were isolated from a Jordanian aquatic region, purified, and identified based on the 18S rRNA and Internal Transcribed Spacer (ITS) DNA markers. The lyophilized biomass was extracted by maceration and ultrasonication-assisted shaking, and then the phytoconstituents were identified via HPLC/MS-MS. Cytotoxicity and cell viability assays were performed to evaluate the cytotoxicity of the algal crude extract against normal Human Umbilical Vein Endothelial cell line EA (HUVEC; cat. no. CRL-1730; ATCC), grade IV Prostatic Adenocarcinoma cell line PC3 (CRL-1435), and Human Pancreatic Ductal Adenocarcinoma cell line (PANC1, CRL-1469).</p><p><strong>Results: </strong>The results revealed the presence of several biologically active compounds in the algal aqueous extract, such as fatty acids, amino acids, nucleic acids, terpenoids, coumarins, flavonoids, and polyphenols such as scopoletin, gingerol, and tanacetol. The MTT assays revealed a biocompatibility of the natural remedy with the normal cell line HUVEC, and a dose-related response pattern was observed against cancerous Pancreatic and Prostatic Adenocarcinoma cell lines. The computed IC50 for Pancreatic, Prostatic, and Normal Epithelial cells was 47.7, 56.3, and 217.5 mg/mL, respectively.</p><p><strong>Discussion: </strong>The richness of bioactive compounds that are classified into diverse secondary metabolite families indicates their potential biological and pharmacological activities. The MTT assay results indicate selective cytotoxicity of the extract against Prostatic and Pancreatic cancer cell lines, with the latter showing more sensitivity to the treatment. The high IC50 values of the normal epithelial cell line express its resistance; therefore, the treatment is biocompatible.</p><p><strong>Conclusion: </strong>Green microalgae, with their bioactive components, could be a promising approach for a sustainable, innovative therapy for Prostatic and Pancreatic cancers; further, advanced research is highly recommended.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsp27 Protects Triple-Negative Breast Cancer Cells against Carboplatin-Induced Cytotoxicity via the Maintenance of Late-Stage Autophagy.","authors":"Mehmet Alper Arslan","doi":"10.2174/0118715206467152260326224634","DOIUrl":"https://doi.org/10.2174/0118715206467152260326224634","url":null,"abstract":"<p><strong>Introduction: </strong>Triple-Negative Breast Cancer (TNBC) is a highly aggressive subtype of breast cancer associated with poor prognosis and limited treatment options. Due to the lack of targetable receptors, standard chemotherapy remains the main treatment for TNBC. Heat shock proteins and (macro)autophagy are fundamental stressresponsive systems involved in oncogenesis and increasingly recognized to act in a coordinated manner. This study aimed to investigate the role of Hsp27 in autophagy regulation in response to carboplatin in TNBC cells.</p><p><strong>Methods: </strong>The IC50 of carboplatin was determined using WST-8 assay. Hsp27 was silenced via siRNA transfection. Autophagic activity was evaluated by Western blot analysis of LC3-II and p62. Cell death was measured using Annexin V-based flow cytometry.</p><p><strong>Results: </strong>Autophagic flux assays conducted with the autophagy inhibitor bafilomycin A1 revealed that Hsp27 depletion blocks the late stage of carboplatin-induced autophagy, as demonstrated by elevated LC3-II levels not further increasing with bafilomycin A1 treatment but remaining unchanged. Additionally, LC3-II accumulation in Hsp27-silenced cells increased in a dose-dependent manner with carboplatin, with 1 mM carboplatin resulting in peak LC3-II levels, accompanied by 50.7% increase in cell death compared to control cells. Collectively, Hsp27 confers cytoprotection against carboplatin-induced toxicity in MDA-MB-231 cells by promoting latestage autophagy.</p><p><strong>Discussion: </strong>Given the aggressive nature of TNBC and its limited treatment options, our findings suggest that targeting Hsp27 has the potential to enhance the efficacy of carboplatin chemotherapy by suppressing cytoprotective autophagy.</p><p><strong>Conclusion: </strong>Our findings demonstrate that depletion of Hsp27 sensitizes human TNBC cells to carboplatininduced cell death through inhibition of late-stage autophagy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acidic Tumor Microenvironment Promotes 5-Fluorouracil Resistance Via Lactate-Driven HIF-1α/MCT4 Activation and Epigenetic Remodeling in Gastric Cancer.","authors":"ZeJi Niu, Tianyu She, XiLi Wu, RuiPing Li","doi":"10.2174/0118715206476991260421062930","DOIUrl":"https://doi.org/10.2174/0118715206476991260421062930","url":null,"abstract":"<p><strong>Introduction: </strong>Tumor acidosis is associated with poor therapeutic response. Yet, it remains unclear whether 5-fluorouracil (5-FU) resistance in gastric cancer is driven by low extracellular pH per se or by lactate as a signaling metabolite.</p><p><strong>Methods: </strong>The human gastric cancer cell line AGS was exposed to extracellular acidosis (pH 6.6; short-term or chronic) or exogenous lactate at neutral pH. 5-FU sensitivity, apoptosis, and lactate production were assessed. Extracellular pH was buffered with 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES); lactate metabolism/ export was disrupted by LDHA inhibition (FX11) or siRNA-mediated MCT4 knockdown. Global histone methylation was analyzed by Western blot, and qPCR quantified H3K4me3 and H3K27me3 occupancy at SLC16A3 (MCT4) and LDHA promoters.</p><p><strong>Results: </strong>Acidosis reduced 5-FU sensitivity, increased lactate output, suppressed apoptosis, and activated hypoxia- inducible factor 1 alpha (HIF-1α)/monocarboxylate transporter 4 (MCT4) signaling. Buffering pH or inhibiting lactate synthesis/export restored 5-FU sensitivity, indicating a reversible, metabolism-dependent phenotype. Under neutral pH, exogenous lactate alone induced reduced 5-FU sensitivity and activated HIF-1α signaling, supporting a pH-independent role for lactate. Acid exposure increased global H3K27me3 and H3K9me3, which normalized after buffering, whereas SLC16A3 and LDHA promoters showed H3K4me3 enrichment with reduced H3K27me3.</p><p><strong>Discussion: </strong>These findings suggest that acidic stress is transduced through lactate signaling to selectively activate chromatin at lactate-metabolism genes, stabilizing an adaptive survival program under chemotherapy.</p><p><strong>Conclusion: </strong>Lactate signaling, rather than low pH alone, underlies a reversible 5-FU-resistant state in gastric cancer cells and may be mitigated by targeting lactate metabolism and/or extracellular pH control.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Egyptian Cobra Venom and Honey Bee Venom Treatment Ameliorated Levels of Neuropilin 1, Angiopoietin 2, and DNA Topoisomerase II Binding Protein 1 in Induced Hepatocellular Carcinoma in Albino Rats.","authors":"Al-Shimaa M Abas, Dina Abdallah Awad, Heba A H Abd Elhameed","doi":"10.2174/0118715206449289260401080709","DOIUrl":"https://doi.org/10.2174/0118715206449289260401080709","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular carcinoma (HCC) is a critical health problem that is classified as the fifth most prevalent malignancy in the world. Our study aimed to investigate the anti-tumor activity of the Egyptian cobra venom and honey bee venom in the treatment of DENA-induced HCC in rats compared to the chemotherapeutic drug cisplatin.</p><p><strong>Methods: </strong>70 male adult albino rats were randomly placed into seven groups. Group 1 served as a negative control. Group 2 received 0.1 LD50 snake venom (SV). Group 3 received 0.1 LD50 bee venom (BV). While the other four groups received diethylnitrosamine (DENA) to induce HCC, they were subsequently divided as follows: Group 4 served as a positive control group (HCC), and the other three remaining groups represented the treated groups. Group 5: snake venom-treated group (HCC+SV). Group 6: bee venom-treated group (HCC+BV). Group 7: Cisplatin-treated group (HCC+CIS).</p><p><strong>Results: </strong>DENA induced HCC, as proved by a significantly high increase in AST, ALT, GGT, and ALP activities and a decrease in total protein and albumin contents. Also, significantly elevated levels of urea, creatinine, proinflammatory cytokine (IL-1β), and tumor markers (NRP1, ANG2, TOPBP1) in comparison to the negative control group. Treatment of HCC rats using snake venom, bee venom, and cisplatin revealed a significant decrease in liver enzymes and tumor markers. The venoms showed a potent synergistic anti-tumor effect by significantly upregulating the expression of pro-apoptotic gene Caspase 3 and downregulating the expression of the anti-apoptotic gene (Bcl-2) in comparison to the positive control HCC group. Our findings were confirmed by histological analysis and immunohistochemical Caspase-3 expression.</p><p><strong>Discussion: </strong>Both snake venom and bee venom have anti-inflammatory, apoptotic, and anticancer effects against induced HCC. However, the use of BV is more effective and safer than SV.</p><p><strong>Conclusion: </strong>Egyptian cobra venom and honey bee venom may serve as an apoptotic stimulator, and can be considered as novel potential therapeutic against HCC.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Study of iNOS and PCNA Expression on the Aggressiveness of Oral Squamous Cell Carcinoma (OSCC).","authors":"Ahmed Noaman Ali, Mohamed Hamdy Sayed, Waleed Mohamed Shaker, Dinesh Rokaya, Mohamed Mohamed Arafa","doi":"10.2174/0118715206457650260306040009","DOIUrl":"https://doi.org/10.2174/0118715206457650260306040009","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Oral Squamous Cell Carcinoma (OSCC) is one of the world's most aggressive cancers. Large-scale NO generation is facilitated by Inducible Nitric Oxide Synthase (iNOS) in chronic inflammatory diseases, including cancer. The 36-kDa non-histone nuclear peptide, also known as Proliferating Cell Nuclear Antigen (PCNA), is important for DNA replication. In human OSCC, iNOS and PCNA are useful indicators of induction, progression, and cell proliferation that influence the aggressiveness and growth rate of cancer. Thus, this study aimed to compare the expression of PCNA and iNOS in various OSCCs.</p><p><strong>Methods: </strong>The study design was a retrospective study using 30 tissue blocks from OSCC patients immunohistochemically stained with iNOS and PCNA antibodies and divided into ten well-differentiated, ten moderatelydifferentiated, and ten poorly-differentiated OSCC. PCNA-positive cells and iNOS infiltration intensity were measured. One-way ANOVA with multiple comparisons was done using Tukey's Post Hoc Test to compare the expression of PCNA and iNOS in various OSCCs, and a Chi-square test was performed for score values in various OSCCs. A P-value < 0.05 was considered significant.</p><p><strong>Results: </strong>With varying histopathological grades of OSCC, the infiltration intensity of iNOS increased from weak expression in well-differentiated OSCC (2.3 ± 0.78) to strong expression in poorly-differentiated OSCC (5 ± 1.18). In addition, PCNA-positive cells were observed and showed higher expression, increasing from weak expression in well-differentiated OSCC (466 ± 31.35) to strong expression in poorly-differentiated OSCC (673 ± 76.27). It was revealed that the expression increased as OSCC progressed (P-value < 0.01).</p><p><strong>Discussion: </strong>The identification of reliable biomarkers that can predict tumor behavior, prognosis, and response to therapy is critical for improving patient outcomes. In this context, they are considered key immunohistopathological markers in OSCC. Understanding the role of iNOS and PCNA in OSCC can enhance diagnostic accuracy and offer new avenues for targeted therapies. These markers may serve not only as tools for evaluating tumor proliferation and invasiveness but also as indicators for therapeutic response, particularly in the context of novel anti-cancer therapies aimed at modulating the tumor microenvironment or cell cycle regulation. Furthermore, their utility in identifying high-risk patients with a propensity to metastasize underscores their clinical relevance in stratifying patient care and informing personalized treatment plans.</p><p><strong>Conclusions: </strong>These results demonstrated that elevated iNOS and PCNA expression may serve as prognostic indicators for OSCC. This will improve clinical decision-making, guiding therapeutic interventions and enhancing patient prognosis in OSCC management.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147979781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photoactivated Aluminium Phthalocyanine Drives Oxidative Stress and Apoptosis in Human Oesophageal Cancer Stem Cells.","authors":"Onyisi Christiana Didamson, Heidi Abrahamse","doi":"10.2174/0118715206432225260121092716","DOIUrl":"https://doi.org/10.2174/0118715206432225260121092716","url":null,"abstract":"<p><strong>Introduction: </strong>Photodynamic therapy (PDT), a light-based treatment strategy, has demonstrated efficiency against several cancers. However, the therapeutic effect of aluminium phthalocyanine chloride tetrasulfonate (AlPcS4Cl)-mediated PDT, which induces oxidative stress and potentiates apoptotic activity in oesophageal Cancer Stem Cells (CSCs), is limited. Therefore, this study examined the effects of AlPcS4Cl in promoting oxidative stress and apoptotic cell death in oesophageal CSCs.</p><p><strong>Methods: </strong>The CSCs were isolated from HKESC-1 cells and were categorised into control and treatment groups. The CSCs treatment groups were exposed to AlPcS4Cl. Twenty-four hours after PDT, the effects of AlPcS4Cl on oesophageal CSCs in inhibiting cell growth, promoting oxidative stress, and cell death were evaluated. Cell viability was assessed using a viability assay. A cellular Reactive Oxygen Species (ROS) assay was used to determine the induction of oxidative stress. Rhodamine-123 flow cytometry analysis was performed to evaluate mitochondrial membrane potential. The Annexin V-FITC/PI assay was used to investigate the cell death mechanism, and a Caspase-Glo 3/7 luminescence assay was employed to assess caspase activities.</p><p><strong>Results: </strong>The results showed altered cell morphology, increased cytotoxicity, decreased cell viability, high ROS generation, impaired mitochondrial membrane, induced apoptosis, and increased caspase 3/7 activity in oesophageal CSCs treated with AlPcS4Cl-PDT compared to the control cells.</p><p><strong>Discussion: </strong>The finding implies that AlPcS4Cl-PDT promotes oxidative stress and apoptosis in oesophageal CSCs, supporting its application for the elimination of CSCs and as an effective anticancer agent.</p><p><strong>Conclusion: </strong>This study demonstrates the promising use of AlPcS4Cl-PDT in eradicating oesophageal CSCs and improving prognosis.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147979755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network Pharmacology, Molecular Docking, and Wnt Signaling-Associated Gene Expression Modulation Effects of New Anti-Colorectal Cancer Agents.","authors":"Manikandan Alagumuthu, Ramprasath Rajavel, Sagufta Patel","doi":"10.2174/0118715206437348260112103124","DOIUrl":"https://doi.org/10.2174/0118715206437348260112103124","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal Cancer (CRC) remains a major global health challenge due to the emergence of resistance to current therapies. Identifying selective compounds that effectively trigger apoptosis in cancer cells while sparing normal tissues is therefore essential.</p><p><strong>Methods: </strong>Candidate molecules were identified through virtual screening and network-based prioritization targeting p53, BAX, and BCL-2. Molecular docking and Molecular Dynamics (MD) simulations were used to validate binding stability and target specificity. In vitro assays were conducted on human CRC (HCT116) and normal colon fibroblast (CCD-18Co) cells to evaluate cytotoxicity, proliferation, and DNA fragmentation. QRTPCR performed gene expression analyses of p53, BAX, and BCL-2 following treatment with 25-100 μg/mL of each compound for 12-72 h.</p><p><strong>Results: </strong>Among the screened compounds, LC_60 emerged as the most potent and selective candidate, exhibiting a remarkably low IC₂⁽ (0.0128 μg/mL) toward HCT116 cells and negligible toxicity toward CCD-18Co cells (CC₂⁽ = 125 μg/mL), yielding an exceptionally high selectivity index (SI ≈ 9,766). Docking and MD simulations confirmed strong and stable interactions of LC_60 with BAX and β-catenin, supporting its dual role in apoptosis induction and Wnt pathway inhibition. LC_60 treatment significantly upregulated p53 and BAX while downregulating BCL-2, consistent with activation of intrinsic apoptotic signaling.</p><p><strong>Discussion: </strong>LC_60's pronounced potency and outstanding selectivity underscore its ability to selectively modulate apoptosis in malignant colon cells while sparing normal fibroblasts, suggesting a strong therapeutic window and tumor specificity.</p><p><strong>Conclusion: </strong>Collectively, the findings identify LC_60 as a highly selective, multitargeted lead compound that activates p53-BAX-mediated apoptosis and inhibits oncogenic Wnt signaling, establishing it as a promising scaffold for further preclinical development in colorectal cancer management.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Frontiers in Prostate Cancer Diagnostics: Nanolaser-Guided Nanotechnology and Computational Biology for Biomarker Surveillance.","authors":"Shikha Baghel Chauhan, Indu Singh, Yash Kalra, Chirag Jain","doi":"10.2174/0118715206411800251120063157","DOIUrl":"https://doi.org/10.2174/0118715206411800251120063157","url":null,"abstract":"<p><strong>Introduction: </strong>Prostate cancer remains a leading cause of cancer-related mortality in men, with early and accurate diagnosis being crucial for effective management. This review explores the convergence of nanolaser- assisted nanotechnology and computational biology as innovative strategies for biomarker surveillance in prostate cancer.</p><p><strong>Methods: </strong>A systematic review of recent peer-reviewed literature from PubMed, Scopus, and Web of Science was conducted, focusing on studies published between 2015 and 2024. Keywords included \"prostate cancer,\" \"nanolaser diagnostics,\" \"nanotechnology,\" \"computational biology,\" and \"biomarker detection.\" Selected articles were analyzed for advancements in diagnostic platforms, biomarker sensitivity, and integration with computational models.</p><p><strong>Results: </strong>Findings indicate that nanolaser-guided nanotechnologies offer ultra-sensitive detection of prostatespecific antigen and emerging molecular biomarkers with improved specificity compared to conventional assays. Computational biology approaches, including machine learning and systems biology models, enhance data interpretation, enable multi-biomarker integration, and support predictive analytics. Hybrid systems demonstrate potential for real-time monitoring, non-invasive sampling, and precision diagnostics.</p><p><strong>Discussion: </strong>The integration of nanolaser technologies with computational biology addresses key limitations of current diagnostic practices, including false positives, delayed detection, and limited biomarker scope. However, challenges such as scalability, regulatory approval, and standardization remain significant barriers. Collaborative research that bridges engineering, computational sciences, and clinical oncology is essential to translate these technologies into practice.</p><p><strong>Conclusion: </strong>Nanolaser-guided nanotechnology, coupled with computational biology, represents a promising frontier in prostate cancer diagnostics. Together, these tools hold the potential to advance biomarker surveillance, improve diagnostic accuracy, and pave the way for personalized oncology.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Cellular Senescence in Melanoma: Implications for Tumor Progression and Therapy.","authors":"Huixin Pan, Jinliang Jiang, Jing Zhang, Zixuan Jia, Qinglu Wang, Jie Zhang, Ying Luo, Bo Yu","doi":"10.2174/0118715206415214251015092820","DOIUrl":"https://doi.org/10.2174/0118715206415214251015092820","url":null,"abstract":"<p><strong>Introduction: </strong>Aging is the most significant risk factor for cancer, with melanoma incidence and mortality rising with advancing age. Cellular senescence, a hallmark of aging, plays dual roles in melanoma progression, exerting both tumor-suppressive and tumor-promoting effects via the senescence-associated secretory phenotype (SASP) and its complex influence on the tumor microenvironment (TME).</p><p><strong>Methods: </strong>Relevant literature was retrieved from PubMed, Web of Science, and Scopus from 2002 up to June 2025, using keywords related to melanoma, cellular senescence, SASP, senolytics, and immunotherapy. Studies were evaluated for mechanistic insights, preclinical evidence, and translational relevance.</p><p><strong>Results: </strong>Evidence indicates that senescent cells in melanoma can suppress tumor growth through cell cycle arrest and immune activation, yet also promote immune evasion, metastasis, and therapy resistance through SASP-mediated pathways. Traditional and targeted therapies can induce senescence, while senolytic agents, particularly in combination with immune checkpoint inhibitors, show promise in eliminating therapy-induced senescent cells and enhancing anti-tumor immunity in preclinical models.</p><p><strong>Discussion: </strong>The therapeutic potential of senescence modulation in melanoma is tempered by key challenges, including the pronounced heterogeneity of senescent cells, SASP's context-dependent effects, and limited melanoma- specific clinical trial data. Strategies to overcome these hurdles include biomarker-driven patient selection, senomorphic modulation, and rational senolytic-immunotherapy combinations.</p><p><strong>Conclusion: </strong>Senescence-targeting strategies hold considerable promise for melanoma treatment but require deeper mechanistic characterization and robust early-phase clinical evaluation before routine clinical application. Integrating senescence modulation into precision oncology frameworks may ultimately improve outcomes in melanoma patients.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Characterization of PEGylated β-Carotene-Loaded Liposomes as Radiosensitizers in HepG2 Hepatocellular Carcinoma Cells: In Vitro and In Silico Studies.","authors":"Habiba Abdel-Moamen, Eman R Abbase, Manal F El-Khadragy, Seifeldin Elabed, Gehad E Elshopakey, Ahmed E Abdel Moneim, Medhat W Shafaa","doi":"10.2174/0118715206430772260121073200","DOIUrl":"https://doi.org/10.2174/0118715206430772260121073200","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular Carcinoma (HCC) is a leading cause of cancer death with limited responsiveness to radiotherapy. β-Carotene has chemopreventive properties, but its clinical use is hindered by poor aqueous solubility and instability. This study developed PEGylated β-carotene-loaded liposomes (PEGLipo- β-Car) as a novel nanocarrier-based radiosensitizer and used in silico modeling to explore its molecular interactions.</p><p><strong>Methods: </strong>PEG-Lipo-β-Car was prepared via thin-film hydration and characterized (TEM, DLS, FTIR, DSC). Cytotoxicity and radiosensitization were evaluated in HepG2 cells under γ-irradiation (0, 5, 10 Gy) using MTT assays, with synergy quantified via Combination Indices (CI). Molecular docking assessed β-carotene binding to PARP and ATM.</p><p><strong>Results: </strong>PEG-Lipo-β-Car exhibited good colloidal stability (size: 143.4 ± 8.2 nm, PDI: 0.201, EE >94%). At 10 Gy irradiation, it reduced the IC50 from 29.78 to 0.57 μg/mL, a 52-fold enhancement with strong synergy (CI=0.019). Empty liposomes alone conferred significant radiosensitization (~30-fold). Docking revealed β- carotene binds the catalytic sites of PARP (-9.19 ± 0.37 kcal/mol) and ATM (-10.12 ± 0.36 kcal/mol).</p><p><strong>Discussion: </strong>The observed radiobiological synergy may stem from a combined effect of carrier-mediated membrane perturbation and/or ROS amplification, coupled with the potential inhibition of DNA repair pathways by the delivered β-carotene.</p><p><strong>Conclusions: </strong>PEGylation enhances β-carotene's stability and radiosensitizing efficacy in HCC cells through a combined mechanism involving carrier effects and potential interference with PARP- and ATM-mediated DNA repair. PEG-Lipo-β-Car is a promising candidate for future preclinical evaluation in hepatocellular carcinoma radiotherapy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147969585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}